Renal L-2-hydroxyglutarate dehydrogenase activity promotes hypoxia tolerance and mitochondrial metabolism in Drosophila melanogaster.

Objectives: The mitochondrial enzyme L-2-hydroxyglutarate dehydrogenase (L2HGDH) regulates the abundance of L-2-hydroxyglutarate (L-2HG), a potent signaling metabolite capable of influencing chromatin architecture, mitochondrial metabolism, and cell fate decisions. Loss of L2hgdh activity in humans induces ectopic L-2HG accumulation, resulting in neurodevelopmental defects, altered immune cell function, and enhanced growth of clear cell renal cell carcinomas. To better understand the molecular mechanisms that underlie these disease pathologies, we used the fruit fly Drosophila melanogaster to investigate the endogenous functions of L2hgdh.

Both enantiomers of β-aminoisobutyric acid BAIBA regulate Fgf23 via MRGPRD receptor by activating distinct signaling pathways in osteocytes.

With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23), urine phosphate, and the muscle metabolite L-β-aminoisobutyric acid (L-BAIBA), suggesting that L-BAIBA may play a role in phosphate metabolism. Here, we show that L-BAIBA increases in serum with exercise and elevates Fgf23 in osteocytes.

l-2-Hydroxyglutarate remodeling of the epigenome and epitranscriptome creates a metabolic vulnerability in kidney cancer models.

Tumor cells are known to undergo considerable metabolic reprogramming to meet their unique demands and drive tumor growth. At the same time, this reprogramming may come at a cost with resultant metabolic vulnerabilities. The small molecule l-2-hydroxyglutarate (l-2HG) is elevated in the most common histology of renal cancer.

The oncometabolite L-2-hydroxyglutarate is a common product of dipteran larval development.

The oncometabolite L-2-hydroxyglutarate (L-2HG) is considered an abnormal product of central carbon metabolism that is capable of disrupting chromatin architecture, mitochondrial metabolism, and cellular differentiation. Under most circumstances, mammalian tissues readily dispose of this compound, as aberrant L-2HG accumulation induces neurometabolic disorders and promotes renal cell carcinomas. Intriguingly, Drosophila melanogaster larvae were recently found to accumulate high L-2HG levels under normal growth conditions, raising the possibility that L-2HG plays a unique role in insect metabolism.

Immediate post-breakfast physical activity improves interstitial postprandial glycemia: a comparison of different activity-meal timings.

The optimal timing between meal ingestion and simple physical activity for improving blood glucose control is unknown. This study compared the effects of physical activity on postprandial interstitial glucose responses when the activity was conducted either immediately before, immediately after, or 30 min after breakfast. Forty-eight adults were randomized to three separate physical activity interventions: standing still (for 30 min), walking (for 30 min), and bodyweight exercises (3 sets of 10 squats, 10 push-ups, 10 lunges, 10 sit-ups).

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group: Report 3: Baseline Retinopathy and Clinical Features Predict Progression of Diabetic Retinopathy.

Purpose: To determine the time and risk factors for developing proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH).

Design: Multicenter, national cohort study.

Methods: Anonymized data of 50 254 patient eyes with diabetes mellitus at 19 UK hospital eye services were extracted at the initial and follow-up visits between 2007 and 2014.

The UK Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group, Report 2: real-world data for the impact of cataract surgery on diabetic macular oedema.

Aim: To assess the rate of 'treatment-requiring diabetic macular oedema (DMO)' in eyes for the two  years before and after cataract surgery.

Methods: Multicentre national diabetic retinopathy (DR) database study with anonymised data extraction across 19 centres from an electronic medical record system.

Inclusion Criteria: eyes undergoing cataract surgery in patients with diabetes with no history of DMO prior to study start.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group, Report 1: baseline characteristics and visual acuity outcomes in eyes treated with intravitreal injections of ranibizumab for diabetic macular oedema.

Aims: To describe baseline characteristics and visual outcome for eyes treated with ranibizumab for diabetic macular oedema (DMO) from a multicentre database.

Methods: Structured clinical data were anonymised and extracted from an electronic medical record from 19 participating UK centres: age at first injection, ETDRS visual acuity (VA), number of injections, ETDRS diabetic retinopathy (DR) and maculopathy grade at baseline and visits. The main outcomes were change in mean VA from baseline, number of injections and clinic visits and characteristics affecting VA change and DR grade.

A fluid mechanical explanation of the spontaneous reattachment of a previously detached Descemet membrane.

Descemet membrane detachment (DMD) is a rare but potentially serious surgical complication that arises most often during cataract surgery. A recent study (Couch, S. M.

The Peterborough scheme for community specialist optometrists in glaucoma: a feasibility study.

Purpose: This study assessed the role of specialist optometrists who were working in the community and sharing the care for glaucoma patients with, and under close supervision of, a consultant ophthalmologist working in the Hospital Eye Services (HES) to ensure high-quality standards, safety, and care.

Methods: From February 2005 onwards, the majority of all new glaucoma referrals to our eye department were diverted to our specialist optometrists in glaucoma (SOGs) in their own community practices. Selected patients in the HES setting who were already diagnosed with stable glaucoma were also transferred to the SOGs.

Fluid mechanics of the human eye: aqueous humour flow in the anterior chamber.

We consider and compare the various different kinds of flow that may take place in the anterior chamber of a human eye. The physical mechanisms responsible for causing such flows may be classified as follows: (i) buoyancy-driven flow arising from the temperature difference between the anterior surface of the cornea and the iris, (ii) flow generated by the aqueous production of the ciliary body, (iii) flow generated by the interaction between buoyancy and gravity while sleeping while sleeping in a face-up position, (iv) flow generated by phakodenesis (lens tremor), (v) flow generated by Rapid Eye Movement (REM) during sleep. Each flow is studied using a traditional fluid mechanics/asymptotic analysis approach.

The management of primary rhegmatogenous retinal detachment not involving the fovea.

Aim: To establish the likelihood of, and risk factors associated with, progression of 'macula-on' retinal detachment.

Methods: A multi-centre prospective observational study of patients with acute retinal detachment, not involving the fovea, was conducted over a 6-month period. Data collected included duration of symptoms, visual acuity, presence of posterior vitreous detachment, retinal drawings and subretinal fluid (SRF) distance from the fovea at a minimum of two time points.

Mathematical model of the spinning of microstructured fibres.

We construct a fluid mechanics model of the drawing of microstructured optical fibres ('holey fibres'). This model can be used to understand and quantify methods for controlling the fibre geometry. The effects of preform rotation are included to examine methods for reducing fibre birefringence.

Prospective survey of adverse reactions to topical antiglaucoma medications in a hospital population.

Aim: To identify the relative incidence and profile of adverse drug reaction (ADR) to various topical ocular hypotensives in a hospital setting.

Methods: All the patients presenting in outpatients clinic and accident and emergency with an ADR to topical hypotensive agent from August 2000 to January 2001 were included in the study. Details regarding the type date of commencing the treatment, the date of developing ADR, time to resolution of the ADR were noted.

Modelling drainage of the precorneal tear film after a blink.

We study the drainage of the precorneal tear film in humans. A fluid dynamic model for the drainage of the aqueous layer is developed that includes the effects of evaporation and gravity. The model may be reduced to a single nonlinear partial differential equation for the thickness of the aqueous layer.

The use of botulinum toxin A in the treatment of functional epiphora.

Aim: The purpose of this study was to investigate the hitherto undescribed effects of botulinum toxin A injected into the lacrimal gland in patients with functional epiphora.

Methods: A prospective non-comparative interventional case series study was designed to include patients with functional epiphora who presented to the Oculoplastic unit at the Wolverhampton and Midland Counties Eye Infirmary. Botulinum toxin A (2.

Fluid flow in the anterior chamber of a human eye.

A simple model is presented to analyse fluid flow in the anterior chamber of a human eye. It is shown that under normal conditions such flow inevitably occurs. The flow, whose reduced Reynolds number is small, is viscosity dominated and is driven by buoyancy effects which are present because of the temperature difference between the front and back of the anterior chamber.

Pars plana vitrectomy with silicone oil in the management of combined rhegmatogenous retinal and choroidal detachment.

Purpose: Rhegmatogenous retinal detachment combined with spontaneous pre-operative choroidal detachment (RDCD) represents a rare but specific entity, which has in the past been associated with a poor prognosis. This study was designed to determine the efficacy of pars plana vitrectomy with silicone oil injection in the management of this very difficult vitreoretinal problem.

Methods: A retrospective analysis was carried out of 13 eyes of 13 consecutive patients who underwent vitrectomy and silicone oil exchange.

The effect of pupil dilation with tropicamide on vision and driving simulator performance.

Purpose: To assess the effect of pupil dilation on vision and driving ability.

Methods: A series of tests on various parameters of visual function and driving simulator performance were performed on 12 healthy drivers, before and after pupil dilation using guttae tropicamide 1%. A driving simulator (Transport Research Laboratory) was used to measure reaction time (RT), speed maintenance and steering accuracy.